A murine model of Chagas' disease is being used to determine the contribution of the immune system to natural resistance to Trypanosoma cruzi and to examine the immune mechanisms important for elimination of parasites. The study of the genetics of resistance to T. cruzi has involved the breeding and challenge of F1, F2, and backcross mice. The influence of the H-2 region on resistance is being evaluated by H-2 typing of the F2 mice and by use of H-2 congenic strains of mice. Bone marrow transfers between resistant and susceptible strains are being done to determine if natural resistance is governed by bone marrow derived cells. Impairment of the immune functions of resistant mice will show which cells of the immune system are necessary for survival. Immune mechanisms important in resistance are identified by transfer of purified cell populations from spleens of immunized mice. The ability of these populations to confer protection is assessed relative to the time of challenge. Passive antibody transfers compare the effectiveness of antibody given at different times and in different amounts on the degree of protection transferred. The differences in parasite strains are evaluated by using cells from mice immunized with one strain and challenged with a different parasite strain. To ensure more reproducibility in our studies, clones of parasites are being produced from several different parasite strains. Characterization of these clones in vivo and in vitro will determine the variability inherent in these parasite strains.